Many polymers have been used in biomedical applications, including polyesters, polyvinyl acetate, polyacrylates, polyorthoesters, and polyanhydrides. One of the advantages of polyesters in such applications is that they are both biodegradable and biocompatible.
Aliphatic polyesters have been widely used in the area of biomaterials for implantable drug delivery devices, sutures, and general tissue supports, after injury or surgery. The polyesters traditionally of greatest interest in the area of biomaterials are derived from lactide, glycolide, and .epsilon.-caprolactone monomers, with a fairly broad range of degradation profiles accessible through various termonomer combinations. The ester linkages in these aliphatic polyesters are hydrolytically and/or enzymatically labile and render the polymers degradable in aqueous environments. However, in many cases it is desirable to produce unique bioerosion profiles outside of the normal range available by in vivo hydrolytic ester cleavage and concomitant solubilization of polyester based implants. Often, more rapid initial degradation, or specific bioerosion/biodegradation profiles are desired. One way to achieve enhanced rates of bioerosion is to select polymers with higher intrinsic solubility/erodability in vivo. However, biodegradable polymers selected for enhanced rate of bioerosion typically have less desirable/structural/chemical characteristics for implant function. One approach to modify enhanced implant degradation profiles has been to substitute anhydride linkages for all or some portion of the ester linkages, along with hydrophobic modifications of the polymer chain to prevent bulk degradation.
In accordance with the present invention, polyester ionomers, salts of carboxy-terminated polyesters, are utilized for implant fabrication. The polyester ionomers exhibit the desired structural/functional characteristics of the polyester, however, with enhanced in vivo solubility, thereby facilitating the solubilization of polymer molecules from the surface of the implant in vivo. Subsequent hydrolysis of the solubilized polyester components in serum at sites removed from the point of implantation, helps to prevent the occurrence of localized pH gradients which can be detrimental to the surrounding tissue viability. Thus, the use of salts of biodegradable carboxy-terminated polyesters in bioerodable implant structures in accordance with the present invention allows fabrication of implants with the needed structural and functional properties, further with good serum solubility of the polyester component.
In accordance with the present invention, polyester ionomers, salts of carboxy-terminated polyesters, are prepared and used as biomaterials for fabrication of implantable constructs for drug delivery and tissue support and reconstruction. The polyester ionomers exhibit good solubility even at higher molecular weights dictated by implant structural/functional requirements. The polyesters are prepared from and degrade into naturally occurring metabolites for enhanced biocompatibility. The polyester ionomers are prepared from the corresponding carboxy-terminated polyesters by neutralization or partial neutralization with biocompatible, pharmaceutically acceptable salt-forming bases. In one aspect of the present invention there is provided compositions comprising biodegradable carboxy-terminated polyesters in combination with the corresponding ionomers. The physical properties of polyester ionomers can be controlled by degree of neutralization of the corresponding carboxy-terminated polyesters and to some extent by selection of the neutralizing base. The polyester ionomers can be used alone or in combination with their carboxy-terminated polyester precursor for use in construction of improved implant matrix compositions for tissue repair and/or prolonged release of biologically active compounds.